Recommendations to Prevent and Control Iron Deficiency in the
United States

Summary

Iron deficiency is the most common known form of nutritional
deficiency. Its prevalence is highest among young children and
women of childbearing age (particularly pregnant women). In
children, iron deficiency causes developmental delays and
behavioral disturbances, and in pregnant women, it increases the
risk for a preterm delivery and delivering a low-birthweight
baby. In the past three decades, increased iron intake among
infants has resulted in a decline in childhood iron-deficiency
anemia in the United States. As a consequence, the use of
screening tests for anemia has become a less efficient means of
detecting iron deficiency in some populations. For women of
childbearing age, iron deficiency has remained prevalent.

To address the changing epidemiology of iron deficiency in
the United States, CDC staff in consultation with experts
developed new recommendations for use by primary health-care
providers to prevent, detect, and treat iron deficiency. These
recommendations update the 1989 "CDC Criteria for Anemia in
Children and Childbearing-Aged Women" (MMWR 1989;38(22):400-4)
and are the first comprehensive CDC recommendations to prevent
and control iron deficiency. CDC emphasizes sound iron nutrition
for infants and young children, screening for anemia among women
of childbearing age, and the importance of low-dose iron
supplementation for pregnant women.
INTRODUCTION

In the human body, iron is present in all cells and has
several vital functions -- as a carrier of oxygen to the tissues
from the lungs in the form of hemoglobin (Hb), as a facilitator
of oxygen use and storage in the muscles as myoglobin, as a
transport medium for electrons within the cells in the form of
cytochromes, and as an integral part of enzyme reactions in
various tissues. Too little iron can interfere with these vital
functions and lead to morbidity and mortality.

In the United States, the prevalence of iron-deficiency
anemia among children declined during the 1970s in association
with increased iron intake during infancy (1-3). Because of this
decline, the value of anemia as a predictor of iron deficiency
has also declined, thus decreasing the effectiveness of routine
anemia screening among children. In contrast, the rate of anemia
among low-income women during pregnancy is high, and no
improvement has been noted since the 1970s (4). These findings,
plus increased knowledge about screening for iron status, raised
questions about the necessity and effectiveness of existing U.S.
programs to prevent and control iron deficiency. CDC requested
the Institute of Medicine to convene an expert committee to
develop recommendations for preventing, detecting, and treating
iron-deficiency anemia among U.S. children and U.S. women of
childbearing age. The committee met throughout 1992, and in 1993
the Institute of Medicine published the committee's
recommendations (5). These guidelines are not practical for all
primary health-care and public health settings, however, because
they require serum ferritin testing during pregnancy (6). This
testing may be appropriate in practices where women consistently
visit their physician throughout pregnancy, but it is less
feasible when analysis of serum ferritin concentration is
unavailable or when prenatal care visits are sporadic. The CDC
recommendations in this report -- including those for pregnant
women -- were developed for practical use in primary health-care
and public health settings.

Beside the Institute of Medicine (5,7), the American Academy
of Pediatrics (8,9), the U.S. Preventive Services Task Force
(10), the American College of Obstetricians and Gynecologists
(9,11), the Federation of American Societies for Experimental
Biology (12), and the U.S. Public Health Service (13) have all
published guidelines within the past 9 years for health-care
providers that address screening for and treatment of iron
deficiency in the United States. Preventing and controlling iron
deficiency are also addressed in Nutrition and Your Health:
Dietary Guidelines for Americans (14).

The CDC recommendations differ from the guidelines published
by the U.S. Preventive Services Task Force (10) in two major
areas. First, the Task Force recommended screening for anemia
among infants at high risk for anemia and pregnant women only.
The CDC recommends periodic screening for anemia among high-risk
populations of infants and preschool children, among pregnant
women, and among nonpregnant women of childbearing age. Second,
the Task Force stated there is insufficient evidence to recommend
for or against iron supplementation during pregnancy, but the CDC
recommends universal iron supplementation to meet the iron
requirements of pregnancy. The CDC recommendations for iron
supplementation during pregnancy are similar to the guidelines
issued by the American Academy of Pediatrics and the American
College of Obstetricians and Gynecologists (9).

This report is intended to provide guidance to primary
health-care providers and emphasizes the etiology and
epidemiology of iron deficiency, the laboratory tests used to
assess iron status, and the screening for and treatment of iron
deficiency at all ages. The recommendations in this report are
based on the 1993 Institute of Medicine guidelines; the
conclusions of an expert panel convened by CDC in April 1994; and
input from public health nutrition program personnel, primary
health-care providers, and experts in hematology, biochemistry,
and nutrition.

National health objective 2.10 for the year 2000 is to
"reduce iron deficiency to less than 3% among children aged 1-4
and among women of childbearing age" (15). The recommendations in
this report for preventing and controlling iron deficiency are
meant to move the nation toward this objective.
BACKGROUND
Iron Metabolism

Total body iron averages approximately 3.8 g in men and 2.3
g in women, which is equivalent to 50 mg/kg body weight for a
75-kg man (16,17) and 42 mg/kg body weight for a 55-kg woman
(18), respectively. When the body has sufficient iron to meet its
needs, most iron (greater than 70%) may be classified as
functional iron; the remainder is storage or transport iron. More
than 80% of functional iron in the body is found in the red blood
cell mass as Hb, and the rest is found in myoglobin and
intracellular respiratory enzymes (e.g., cytochromes)
(Table_1).
Iron is stored primarily as ferritin, but some is stored as
hemosiderin. Iron is transported in blood by the protein
transferrin. The total amount of iron in the body is determined
by intake, loss, and storage of this mineral (16).
Iron Intake

Regulation of iron balance occurs mainly in the
gastrointestinal tract through absorption. When the absorptive
mechanism is operating normally, a person maintains functional
iron and tends to establish iron stores. The capacity of the body
to absorb iron from the diet depends on the amount of iron in the
body, the rate of red blood cell production, the amount and kind
of iron in the diet, and the presence of absorption enhancers and
inhibitors in the diet.

The percentage of iron absorbed (i.e., iron bioavailability)
can vary from less than 1% to greater than 50% (19). The main
factor controlling iron absorption is the amount of iron stored
in the body. The gastrointestinal tract increases iron absorption
when the body's iron stores are low and decreases absorption when
stores are sufficient. An increased rate of red blood cell
production can also stimulate iron uptake severalfold (16,20).

Among adults, absorption of dietary iron averages
approximately 6% for men and 13% for nonpregnant women in their
childbearing years (19). The higher absorption efficiency of
these women reflects primarily their lower iron stores as a
result of menstruation and pregnancy. Among iron-deficient
persons, iron absorption is also high (21). Absorption of iron
increases during pregnancy, but the amount of the increase is not
well defined (6); as iron stores increase postpartum, iron
absorption decreases.

Iron bioavailability also depends on dietary composition.
Heme iron, which is found only in meat, poultry, and fish, is two
to three times more absorbable than non-heme iron, which is found
in plant-based foods and iron-fortified foods (19,20). The
bioavailability of non-heme iron is strongly affected by the kind
of other foods ingested at the same meal. Enhancers of iron
absorption are heme iron (in meat, poultry, and fish) and vitamin
C; inhibitors of iron absorption include polyphenols (in certain
vegetables), tannins (in tea), phytates (in bran), and calcium
(in dairy products) (16,22). Vegetarian diets, by definition, are
low in heme iron. However, iron bioavailability in a vegeterian
diet can be increased by careful planning of meals to include
other sources of iron and enhancers of iron absorption (14). In
the diet of an infant, before the introduction of solid foods,
the amount of iron absorbed depends on the amount and
bioavailability of iron in breast milk or formula (8)
(Table_2).
Iron Turnover and Loss

Red blood cell formation and destruction is responsible for
most iron turnover in the body. For example, in adult men,
approximately 95% of the iron required for the production of red
blood cells is recycled from the breakdown of red blood cells and
only 5% comes from dietary sources. In contrast, an infant is
estimated to derive approximately 70% of red blood cell iron from
the breakdown of red blood cells and 30% from the diet (23).

In adults, approximately 1 mg of iron is lost daily through
feces and desquamated mucosal and skin cells (24). Women of
childbearing age require additional iron to compensate for
menstrual blood loss (an average of 0.3-0.5 mg daily during the
childbearing years) (18) and for tissue growth during pregnancy
and blood loss at delivery and postpartum (an average of 3 mg
daily over 280 days' gestation) (25). In all persons, a minute
amount of iron is lost daily from physiological gastrointestinal
blood loss. Pathological gastrointestinal iron loss through
gastrointestinal bleeding occurs in infants and children
sensitive to cow's milk and in adults who have peptic ulcer
disease, inflammatory bowel syndrome, or bowel cancer. Hookworm
infections, although not common in the United States (26), are
also associated with gastrointestinal blood loss and iron
depletion (27).
Iron Stores

Iron present in the body beyond what is immediately needed
for functional purposes is stored as the soluble protein complex
ferritin or the insoluble protein complex hemosiderin (16,17).
Ferritin and hemosiderin are present primarily in the liver, bone
marrow, spleen, and skeletal muscles. Small amounts of ferritin
also circulate in the plasma. In healthy persons, most iron is
stored as ferritin (an estimated 70% in men and 80% in women) and
smaller amounts are stored as hemosiderin (Table_1). When
long-term negative iron balance occurs, iron stores are depleted
before iron deficiency begins.

Men store approximately 1.0-1.4 g of body iron (17,28),
women approximately 0.2-0.4 g (18,28), and children even less
(23). Full-term infants of normal or high birthweight are born
with high body iron (an average of 75 mg/kg body weight), to
which iron stores contribute approximately 25% (23). Preterm or
low-birthweight infants are born with the same ratio of total
body iron to body weight, but because their body weight is low,
the amount of stored iron is low too.
Manifestations of Iron Deficiency

Iron deficiency is one of the most common nutritional
deficiencies worldwide (29) and has several causes (Exhibit 1)
(Table_1B). Iron deficiency represents a spectrum (Table_3)
ranging from iron depletion, which causes no physiological
impairments,
to iron-deficiency anemia, which affects the functioning of several
organ systems. In iron depletion, the amount of stored iron
(e.g., as measured by serum ferritin concentration) is reduced
but the amount of functional iron may not be affected (30,31).
Persons who have iron depletion have no iron stores to mobilize
if the body requires more iron. In iron-deficient erythropoiesis,
stored iron is depleted and transport iron (e.g., as measured by
transferrin saturation) is reduced further; the amount of iron
absorbed is not sufficient to replace the amount lost or to
provide the amount needed for growth and function. In this stage,
the shortage of iron limits red blood cell production and results
in increased erthryocyte protoporphyrin concentration. In
iron-deficiency anemia, the most severe form of iron deficiency,
the shortage of iron leads to underproduction of iron-containing
functional compounds, including Hb. The red blood cells of
persons who have iron-deficiency anemia are microcytic and
hypochromic (30,31).

In infants (persons aged 0-12 months) and preschool children
(persons aged 1-5 years), iron-deficiency anemia results in
developmental delays and behavioral disturbances (e.g., decreased
motor activity, social interaction, and attention to tasks)
(32,33). These developmental delays may persist past school age
(i.e., 5 years) if the iron deficiency is not fully reversed
(32-34).
In these studies of development and behavior,
iron-deficiency anemia was defined as a Hb concentration of less
than or equal to 10.0 g/dL or less than or equal to 10.5 g/dL;
further study is needed to determine the effects of mild
iron-deficiency anemia (for example, a Hb concentration of
greater than 10.0 g/dL but less than 11.0 g/dL in children aged
1- less than 2 years) on infant and child development and
behavior. Iron-deficiency anemia also contributes to lead
poisoning in children by increasing the gastrointestinal tract's
ability to absorb heavy metals, including lead (35).
Iron-deficiency anemia is associated with conditions that may
independently affect infant and child development (e.g., low
birthweight, generalized undernutrition, poverty, and high blood
level of lead) that need to be taken into account when
interventions addressing iron-deficiency anemia are developed and
evaluated (34).

In adults (persons aged greater than or equal to 18 years),
iron-deficiency anemia among laborers (e.g., tea pickers, latex
tappers, and cotton mill workers) in the developing world impairs
work capacity; the impairment appears to be at least partially
reversible with iron treatment (36,37). It is not known whether
iron-deficiency anemia affects the capacity to perform less
physically demanding labor that is dependent on sustained
cognitive or coordinated motor function (37).

Among pregnant women, iron-deficiency anemia during the
first two trimesters of pregnancy is associated with a twofold
increased risk for preterm delivery and a threefold increased
risk for delivering a low-birthweight baby (38). Evidence from
randomized control trials indicates that iron supplementation
decreases the incidence of iron-deficiency anemia during
pregnancy (10,39-42), but trials of the effect of universal iron
supplementation during pregnancy on adverse maternal and infant
outcomes are inconclusive (10,43,44).
Risk for and Prevalence of Iron Deficiency in the United States

A rapid rate of growth coincident with frequently inadequate
intake of dietary iron places children aged less than 24 months,
particularly those aged 9-18 months, at the highest risk of any
age group for iron deficiency (3). The iron stores of full-term
infants can meet an infant's iron requirements until ages 4-6
months, and iron-deficiency anemia generally does not occur until
approximately age 9 months. Compared with full-term infants of
normal or high birthweight, preterm and low-birthweight infants
are born with lower iron stores and grow faster during infancy;
consequently, their iron stores are often depleted by ages 2-3
months (5,23) and they are at greater risk for iron deficiency
than are full-term infants of normal or high birthweight. Data
from the third National Health and Nutrition Examination Survey
(NHANES III), which was conducted during 1988-1994, indicated
that 9% of children aged 12-36 months in the United States had
iron deficiency (on the basis of two of three abnormal values for
erythrocyte protoporphyrin concentration, serum ferritin
concentration, and transferrin saturation) and that 3% also had
iron-deficiency anemia (Table_4). The prevalence of iron
deficiency is higher among children living at or below the
poverty level than among those living above the poverty level and
higher among black or Mexican-American children than among white
children (45).

Evidence from the Continuing Survey of Food Intakes by
Individuals (CSFII), which was conducted during 1994-1996,
suggests that most infants meet the recommended dietary allowance
for iron through diet (Table_5; these data exclude breast-fed
infants). However, the evidence also suggests that more than half
of children aged 1-2 years may not be meeting the recommended
dietary allowance for iron through their diet (Table_5; these
data do not include iron intake from supplemental iron).

An infant's diet is a reasonable predictor of iron status in
late infancy and early childhood (23,48). For example,
approximately 20%-40% of infants fed only non-iron-fortified
formula or whole cow's milk and 15%-25% of breast-fed infants are
at risk for iron deficiency by ages 9-12 months (23,48). Infants
fed mainly iron-fortified formula (greater than or equal to 1.0
mg iron/100 kcal formula) (8) are not likely to have iron
deficiency at age 9 months (48). Another study has documented
that intake of iron-fortified cereal protects against iron
deficiency: among exclusively breast-fed infants who were fed
cereal starting at age 4 months, 3% of infants who were
randomized to receive iron-fortified cereal compared with 15% of
infants who were randomized to receive non-iron-fortified cereal
had iron-deficiency anemia at age 8 months (49). The effect of
prolonged exclusive breast feeding on iron status is not well
understood. One nonrandomized study with a small cohort suggested
that exclusive breast feeding for greater than 7 months is
protective against iron deficiency compared with breast feeding
plus the introduction of non-iron-fortified foods at age less
than or equal to 7 months (50); infants weaned to iron-fortified
foods were not included in this study.

Early introduction (i.e., before age 1 year) of whole cow's
milk and consumption of greater than 24 oz of whole cow's milk
daily after the 1st year of life are risk factors for iron
deficiency because this milk has little iron, may replace foods
with higher iron content, and may cause occult gastrointestinal
bleeding (8,48,51,52). Because goat's milk and cow's milk have
similar compositions (53,54), infants fed goat's milk are likely
to have the same risk for developing iron deficiency as do
infants fed cow's milk. Of all milks and formulas, breast milk
has the highest percentage of bioavailable iron, and breast milk
and iron-fortified formulas provide sufficient iron to meet an
infant's needs (55). Iron-fortified formulas are readily
available, do not cost much more than non-iron-fortified
formulas, and have few proven side effects except for darker
stools (56,57). Controlled trials and observational studies have
indicated that iron-fortified formula causes no more
gastrointestinal distress than does non-iron-fortified formula
(56-58), and there is little medical indication for
non-iron-fortified formula (59).

After age 24 months, when the growth rate of children slows
and the diet becomes more diversified, the risk for iron
deficiency drops (28,45,47). In children aged greater than 36
months, dietary iron and iron status are usually adequate
(45,47). For these older children, risks for iron deficiency
include limited access to food (e.g., because of low family
income (45) or because of migrant or refugee status), a low-iron
or other specialized diet, and medical conditions that affect
iron status (e.g., inflammatory or bleeding disorders) (3).

During adolescence (ages 12- less than 18 years), iron
requirements (46) and hence the risk for iron deficiency increase
because of rapid growth (60,61). Among boys, the risk subsides
after the peak pubertal growth period. Among girls and women,
however, menstruation increases the risk for iron deficiency
throughout the childbearing years. An important risk factor for
iron-deficiency anemia among nonpregnant women of childbearing
age is heavy menstrual blood loss (greater than or equal to 80
mL/month) (18), which affects an estimated 10% of these women in
the United States (17,18). Other risk factors include use of an
intrauterine device (which is associated with increased menstrual
blood loss), high parity, previous diagnosis of iron-deficiency
anemia, and low iron intake (45,60). Use of oral contraceptives
is associated with decreased risk for iron deficiency (18,62).

Data from CSFII suggest that only one fourth of adolescent
girls and women of childbearing age (12-49 years) meet the
recommended dietary allowance for iron through diet (Table_5).
Indeed, data from the complete NHANES III indicated that 11% of
nonpregnant women aged 16-49 years had iron deficiency and that
3%-5% also had iron-deficiency anemia (Table_4).

Among pregnant women, expansion of blood volume by
approximately 35% and growth of the fetus, placenta, and other
maternal tissues increase the demand for iron threefold in the
second and third trimesters to approximately 5.0 mg iron/day
(18,46). Although menstruation ceases and iron absorption
increases during pregnancy, most pregnant women who do not take
iron supplements to meet increased iron requirements during
pregnancy cannot maintain adequate iron stores, particularly
during the second and third trimesters (63). After delivery, the
iron in the fetus and placenta is lost to the woman, but some of
the iron in the expanded blood volume may be returned to the
woman's iron stores (18).

The prevalence of anemia in low-income, pregnant women
enrolled in public health programs in the United States has
remained fairly stable since 1979 (4). In 1993, the prevalence of
anemia among these women was 9%, 14%, and 37% in the first,
second, and third trimesters, respectively (4). Comparable data
for the U.S. population of all pregnant women are unavailable.
The low dietary intake of iron among U.S. women of childbearing
age (47), the high prevalence of iron deficiency and
iron-deficiency anemia among these women (45), and the increased
demand for iron during pregnancy (18,46) suggest that anemia
during pregnancy may extend beyond low-income women.

Published data on iron supplement use by a representative
sample of pregnant U.S. women are limited. In the 1988 National
Maternal and Infant Health Survey of a nationally representative
sample of U.S. women who delivered a child in that year, 83% of
respondents reported that they took supplements with multiple
vitamins and minerals greater than or equal to 3 days/week for 3
months after they found out they were pregnant (64).
Significantly smaller percentages of black women; Eskimo, Aleut,
or American Indian women; women aged less than 20 years; and
women having less than a high school education reported taking
these supplements. In this survey, self-reported use of
supplementation was within the range (55%-95%) found in a review
of studies using objective measures to estimate adherence (e.g.,
pill counts and serum ferritin concentration) (65). The survey
results suggest that the groups of women at high risk for iron
deficiency during nonpregnancy are less likely to take
supplements with multiple vitamins and minerals during pregnancy.
This survey did not question respondents about changes in
supplement use during pregnancy or what dose of iron supplements
was consumed.

In the United States, the main reasons for lack of a
recommended iron supplementation regimen during pregnancy may
include lack of health-care provider and patient perceptions that
iron supplements improve maternal and infant outcomes (65),
complicated dose schedules (5,65), and uncomfortable side effects
(e.g., constipation, nausea, and vomiting) (66,67). Low-dose
supplementation regimens that meet pregnancy requirements (i.e.,
30 mg iron/day) (46) and reduce unwanted side effects are as
effective as higher dose regimens (i.e., 60 or 120 mg iron/day)
in preventing iron-deficiency anemia (66). Simplified dose
schedules (e.g., 1 dose/day) may also improve compliance (65).
Methods to improve compliance among pregnant women at high risk
for iron deficiency require further study.

Among men (males aged greater than or equal to 18 years) and
postmenopausal women in the United States, iron-deficiency anemia
is uncommon. Data from NHANES III indicated that less than or
equal to 2% of men aged greater than or equal to 20 years and 2%
of women aged greater than or equal to 50 years had
iron-deficiency anemia (Table_4). Data from CFSII indicate that
most men and most women aged greater than or equal to 50 years
meet the recommended dietary allowance for iron through diet
(Table_5). In a study of adults having iron-deficiency anemia,
62% had clinical evidence of gastrointestinal bleeding as a
result of lesions (e.g., ulcers and tumors) (68). In NHANES I,
which was conducted during 1971-1975, about two thirds of anemia
cases among men and postmenopausal women were attributable to
chronic disease or inflammatory conditions (69). The findings of
these studies suggest that, among these populations, the primary
causes of anemia are chronic disease and inflammatory conditions
and that low iron intake should not be assumed to be the cause of
the anemia.
TESTS USED TO ASSESS IRON STATUS

Iron status can be assessed through several laboratory
tests. Because each test assesses a different aspect of iron
metabolism, results of one test may not always agree with results
of other tests. Hematological tests based on characteristics of
red blood cells (i.e., Hb concentration, hematocrit, mean cell
volume, and red blood cell distribution width) are generally more
available and less expensive than are biochemical tests.
Biochemical tests (i.e., erythrocyte protoporphyrin
concentration, serum ferritin concentration, and transferrin
saturation), however, detect earlier changes in iron status.

Although all of these tests can be used to assess iron
status, no single test is accepted for diagnosing iron deficiency
(70). Detecting iron deficiency in a clinical or field setting is
more complex than is generally believed.

Lack of standardization among the tests and a paucity of
laboratory proficiency testing limit comparison of results
between laboratories (71). Laboratory proficiency testing is
currently available for measuring Hb concentration, hematocrit,
red blood cell count, serum ferritin concentration, and serum
iron concentration; provisional proficiency testing was added in
1997 for total iron-binding capacity in the College of American
Pathologists survey and was added to the American Association of
Bioanalysts survey in 1998. As of April 1998, three states (New
York, Pennsylvania, and Wisconsin) had proficiency testing
programs for erthrocyte protoporphryin concentration. Regardless
of whether test standardization and proficiency testing become
routine, better understanding among health-care providers about
the strengths and limitations of each test is necessary to
improve screening for and diagnosis of iron-deficiency anemia,
especially because the results from all of these tests can be
affected by factors other than iron status.

Only the most common indicators of iron deficiency are
described in this section. Other indicators of iron deficiency
(e.g., unbound iron-binding capacity and the concentrations of
transferrin receptor, serum transferrin, and holo-ferritin) are
less often used or are under development.
Hb Concentration and Hematocrit

Because of their low cost and the ease and rapidity in
performing them, the tests most commonly used to screen for iron
deficiency are Hb concentration and hematocrit (Hct). These
measures reflect the amount of functional iron in the body. The
concentration of the iron-containing protein Hb in circulating
red blood cells is the more direct and sensitive measure. Hct
indicates the proportion of whole blood occupied by the red blood
cells; it falls only after the Hb concentration falls. Because
changes in Hb concentration and Hct occur only at the late stages
of iron deficiency, both tests are late indicators of iron
deficiency; nevertheless, these tests are essential for
determining iron-deficiency anemia.

Because iron deficiency is such a common cause of childhood
anemia, the terms anemia, iron deficiency, and iron-deficiency
anemia are often used interchangeably (3). The only cases of
anemia that can be classified as iron-deficiency anemia, however,
are those with additional evidence of iron deficiency. The
concept of a close association between anemia and iron deficiency
is closest to correct when the prevalence of iron deficiency is
high. In the United States, the prevalence and severity of anemia
have declined in recent years; hence, the proportion of anemia
due to causes other than iron deficiency has increased
substantially. As a consequence, the effectiveness of anemia
screening for iron deficiency has decreased in the United States.

Iron deficiency may be defined as absent bone marrow iron
stores (as described on bone marrow iron smears), an increase in
Hb concentration of greater than 1.0 g/dL after iron treatment,
or abnormal values on certain other biochemical tests (17). The
recent recognition that iron deficiency seems to have general and
potentially serious negative effects (32-34) has made identifying
persons having iron deficiency as important as identifying
persons having iron-deficiency anemia.

The case definition of anemia recommended in this report is
less than 5th percentile of the distribution of Hb concentration
or Hct in a healthy reference population and is based on age,
sex, and (among pregnant women) stage of pregnancy (45,72). This
case definition for anemia was shown to correctly identify 37% of
women of childbearing age and 25% of children aged 1-5 years who
were iron deficient (defined as two of three positive test
results {i.e., low mean cell volume, high erythrocyte
protoporphyrin, or low transferrin saturation}) (sensitivity) and
to correctly classify 93% of women of childbearing age and 92% of
children aged 1-5 years as not having iron deficiency
(specificity) (73). Lowering the Hb concentration or Hct cut-off
would result in identifying fewer people who have anemia due to
causes other than iron deficiency (false positives) but also in
overlooking more people with iron deficiency (true positives)
(74).

The distributions of Hb concentration and Hct and thus the
cutoff values for anemia differ between children, men,
nonpregnant women, and pregnant women and by age or weeks of
gestation (Table_6). The distributions also differ by altitude,
smoking status, and race.

Among pregnant women, Hb concentration and Hct decline
during the first and second trimesters because of an expanding
blood volume (18,39-42). Among pregnant women who do not take
iron supplements, Hb concentration and Hct remain low in the
third trimester, and among pregnant women who have adequate iron
intake, Hb concentration and Hct gradually rise during the third
trimester toward the prepregnancy levels (39,40). Because
adequate data are lacking in the United States, the cutoff values
for anemia are based on clinical studies of European women who
had taken iron supplementation during pregnancy (39-42,72). For
pregnant women, a test result greater than 3 standard deviations
(SD) higher than the mean of the reference population (i.e., a Hb
concentration of greater than 15.0 g/dL or a Hct of greater than
45.0%), particularly in the second trimester, likely indicates
poor blood volume expansion (72). High Hb concentration or Hct
has been associated with hypertension and poor pregnancy outcomes
(e.g., fetal growth retardation, fetal death, preterm delivery,
and low birthweight) (75-78). In one study, women who had a Hct
of greater than or equal to 43% at 26-30 weeks' gestation had
more than a twofold increased risk for preterm delivery and a
fourfold increased risk for delivering a child having fetal
growth retardation than did women who had a Hct of 33%-36% (76).
Hence, a high Hb concentration or Hct in the second or third
trimester of pregnancy should not be considered an indicator of
desirable iron status.

Long-term residency at high altitude (greater than or equal
to 3,000 ft) (79) and cigarette smoking (80) cause a generalized
upward shift in Hb concentration and Hct (Table_7). The
effectiveness of screening for anemia is lowered if the cutoff
values are not adjusted for these factors (72,79,80). Adjustment
allows the positive predictive value of anemia screening to be
comparable between those who reside near sea-level and those who
live at high altitude and between smokers and nonsmokers (72).

In the United States, the distribution of Hb concentration
values is similar among whites and Asian Americans (81), and the
distribution of Hct values is similar among whites and American
Indians (82). The distributions are lower among blacks than
whites, however, even after adjustment for income (83,84). These
different distributions are not caused by a difference in iron
status indicators (e.g., iron intake, serum ferritin
concentration, or transferrin saturation); thus, applying the
same criteria for anemia to all races results in a higher rate of
false-positive cases of iron deficiency for blacks (84). For
example, in the United States during 1976-1980, 28% of
nonpregnant black women but only 5% of nonpregnant white women
had a Hb concentration of less than 12 g/dL and, according to the
anemia criteria, would be classified as iron deficient, even
though other tests for iron status suggested these women were not
iron deficient (84). For this reason, the Institute of Medicine
recommends lowering Hb concentration and Hct cutoff values for
black children aged less than 5 years by 0.4 g/dL and 1%,
respectively, and for black adults by 0.8 g/dL and 2%,
respectively (5). Because the reason for this disparity in
distributions by race has not been determined, the
recommendations in this report do not provide race-specific
cutoff values for anemia. Regardless, health-care providers
should be aware of the possible difference in the positive
predictive value of anemia screening for iron deficiency among
blacks and whites and consider using other iron status tests
(e.g., serum ferritin concentration and transferrin saturation)
for their black patients.

Accurate, low-cost, clinic-based instruments have been
developed for measuring Hb concentration and Hct by using
capillary or venous blood (85,86). Small diurnal variations are
seen in Hb concentration and Hct measurements, but these
variations are neither biologically nor statistically significant
(87,88). A potential source of error of using capillary blood to
estimate Hb concentration and Hct in screening is improper
sampling technique. For example, excessive squeezing (i.e.,
"milking") of the finger contaminates the blood with tissue
fluid, leading to false low readings (89). Confirmation of a low
reading is recommended by obtaining a second capillary blood
sample from the finger or by venipuncture.

Although measures of Hb concentration and Hct cannot be used
to determine the cause of anemia, a diagnosis of iron-deficiency
anemia can be made if Hb concentration or Hct increases after a
course of therapeutic iron supplementation (23,51).
Alternatively, other laboratory tests (e.g., mean cell volume,
red blood cell distribution width, and serum ferritin
concentration) can be used to differentiate iron-deficiency
anemia from anemia due to other causes.

In the United States in recent years, the usefulness of
anemia screening as an indicator of iron deficiency has become
more limited, particularly for children. Studies using
transferrin saturation (a more sensitive test for iron
deficiency) have documented that iron deficiency in most
subpopulations of children has declined such that screening by Hb
concentration no longer efficiently predicts iron deficiency
(3,45,51,90). Data from NHANES II, which was conducted during
1976-1980, indicated that less than 50% of children aged 1-5
years and women in their childbearing years who had anemia (as
defined by Hb concentration less than 5th percentile) were iron
deficient (i.e., had at least two of the following: low mean cell
volume, high erythrocyte protoporphyrin concentration, or low
transferrin saturation) (70,73,83). Causes of anemia other than
iron deficiency include other nutritional deficiencies (e.g.,
folate or vitamin B12 deficiency), hereditary defects in red
blood cell production (e.g., thalassemia major and sickle cell
disease), recent or current infection, and chronic inflammation
(91). The current pattern of iron-deficiency anemia in the United
States (28,45) indicates that selective anemia screening of
children at known risk for iron deficiency or additional
measurement of indicators of iron deficiency (e.g., erythrocyte
protoporphyrin concentration and serum ferritin concentration) to
increase the positive predictive value of screening are now
suitable approaches to assessing iron deficiency among most U.S.
children (3,73). The costs and feasibility of screening using
additional indicators of iron deficiency may preclude the routine
use of these indicators.
Mean Cell Volume

Mean cell volume (MCV), the average volume of red blood
cells, is measured in femtoliters (10-15 liters). This value can
be calculated as the ratio of Hct to red blood cell count or
measured directly using an electronic counter. MCV is highest at
birth, decreases during the first 6 months of life, then
gradually increases during childhood to adult levels (23,51). A
low MCV corresponds with the 5th percentile for age for the
reference population in NHANES III (28).

Some anemias, including iron-deficiency anemia, result in
microcytic red blood cells; a low MCV thus indicates microcytic
anemia (Table_8). If cases of lead poisoning and the anemias of
infection, chronic inflammatory disease, and thalassemia minor
can be excluded, a low MCV serves as a specific index for
iron-deficiency anemia (28,87,94,95).
Red Blood Cell Distribution Width

Red blood cell distribution width (RDW) is calculated by
dividing the SD of red blood cell volume by MCV and multiplying
by 100 to express the result as a percentage:

RDW (%) = {SD of red blood cell volume (fL)/MCV (fL)} x 100

A high RDW is generally set at greater than 14.0%, which
corresponds to the 95th percentile of RDW for the reference
population in NHANES III (20). The RDW value obtained depends on
the instrument used (51,95).

An RDW measurement often follows an MCV test to help
determine the cause of a low MCV. For example, iron-deficiency
anemia usually causes greater variation in red blood cell size
than does thalassemia minor (96). Thus, a low MCV and an RDW of
greater than 14.0% indicates iron-deficiency anemia, whereas a
low MCV and an RDW less than or equal to 14.0% indicates
thalassemia minor (51).
Erythrocyte Protoporphyrin Concentration

Erythrocyte protoporphyrin is the immediate precursor of Hb.
The concentration of erythrocyte protoporphyrin in blood
increases when insufficient iron is available for Hb production.
A concentration of greater than 30 ug/dL of whole blood or
greater than 70 ug/dL of red blood cells among adults and a
concentration of greater than 80 ug/dL of red blood cells among
children aged 1-2 years indicates iron deficiency (28,45,91). The
normal range of erythrocyte protoporphyrin concentration is
higher for children aged 1-2 years than for adults, but no
consensus exists on the normal range for infants (28,90). The
sensitivity of free erythrocyte protoporphyrin to iron deficiency
(as determined by response to iron therapy) in children and
adolescents aged 6 months-17 years is 42%, and the estimated
specificity is 61% (74).

Infection, inflammation, and lead poisoning as well as iron
deficiency can elevate erythrocyte protoporphyrin concentration
(23,92). This measure of iron status has several advantages and
disadvantages relative to other laboratory measures. For example,
the day-to-day variation within persons for erythrocyte
protoporphyrin concentration is less than that for serum iron
concentration and transferrin saturation (87). A high erythrocyte
protoporphyrin concentration is an earlier indicator of
iron-deficient erythropoiesis than is anemia, but it is not as
early an indicator of low iron stores as is low serum ferritin
concentration (30). Inexpensive, clinic-based methods have been
developed for measuring erythrocyte protoporphyrin concentration,
but these methods can be less reliable than laboratory methods
(92).
Serum Ferritin Concentration

Nearly all ferritin in the body is intracellular; a small
amount circulates in the plasma. Under normal conditions, a
direct relationship exists between serum ferritin concentration
and the amount of iron stored in the body (97), such that 1 ug/L
of serum ferritin concentration is equivalent to approximately 10
mg of stored iron (98). In the United States, the average serum
ferritin concentration is 135 ug/L for men (28), 43 ug/L for
women (28), and approximately 30 ug/L for children aged 6-24
months (23).

Serum ferritin concentration is an early indicator of the
status of iron stores and is the most specific indicator
available of depleted iron stores, especially when used in
conjunction with other tests to assess iron status. For example,
among women who test positive for anemia on the basis of Hb
concentration or Hct, a serum ferritin concentration of less than
or equal to 15 ug/L confirms iron deficiency and a serum ferritin
concentration of greater than 15 ug/L suggests that iron
deficiency is not the cause of the anemia (93). Among women of
childbearing age, the sensitivity of low serum ferritin
concentration (less than or equal to 15 ug/L) for iron deficiency
as defined by no stainable bone marrow iron is 75%, and the
specificity is 98%; when low serum ferritin concentration is set
at less than 12 ug/L, the sensitivity for iron deficiency is 61%
and the specificity is 100% (93). Although low serum ferritin
concentration is an early indicator of low iron stores, it has
been questioned whether a normal concentration measured during
the first or second trimester of pregnancy can predict adequate
iron status later in pregnancy (6).

The cost of assessing serum ferritin concentration and the
unavailability of clinic-based measurement methods hamper the use
of this measurement in screening for iron deficiency. In the
past, methodological problems have hindered the comparability of
measurements taken in different laboratories (87), but this
problem may be reduced by proficiency testing and standardized
methods. Factors other than the level of stored iron can result
in large within-individual variation in serum ferritin
concentration (99). For example, because serum ferritin is an
acute-phase reactant, chronic infection, inflammation, or
diseases that cause tissue and organ damage (e.g., hepatitis,
cirrhosis, neoplasia, or arthritis) can raise its concentration
independent of iron status (97). This elevation can mask depleted
iron stores.
Transferrin Saturation

Transferrin saturation indicates the extent to which
transferrin has vacant iron-binding sites (e.g., a low
transferrin saturation indicates a high proportion of vacant
iron-binding sites). Saturation is highest in neonates, decreases
by age 4 months, and increases throughout childhood and
adolescence until adulthood (23,28). Transferrin saturation is
based on two laboratory measures, serum iron concentration and
total iron-binding capacity (TIBC). Transferrin saturation is
calculated by dividing serum iron concentration by TIBC and
multiplying by 100 to express the result as a percentage:

Serum iron concentration is a measure of the total amount of
iron in the serum and is often provided with results from other
routine tests evaluated by automated, laboratory chemistry
panels. Many factors can affect the results of this test. For
example, the concentration of serum iron increases after each
meal (71), infections and inflammations can decrease the
concentration (69), and diurnal variation causes the
concentration to rise in the morning and fall at night (100). The
day-to-day variation of serum iron concentration within
individuals is greater than that for Hb concentration and Hct
(88,101).

TIBC is a measure of the iron-binding capacity within the
serum and reflects the availability of iron-binding sites on
transferrin (94). Thus, TIBC increases when serum iron
concentration (and stored iron) is low and decreases when serum
iron concentration (and stored iron) is high. Factors other than
iron status can affect results from this test. For example,
inflammation, chronic infection, malignancies, liver disease,
nephrotic syndrome, and malnutrition can lower TIBC readings, and
oral contraceptive use and pregnancy can raise the readings
(87,102). Nevertheless, the day-to-day variation is less than
that for serum iron concentration (87,101). TIBC is less
sensitive to iron deficiency than is serum ferritin
concentration, because changes in TIBC occur after iron stores
are depleted (17,31,94).

A transferrin saturation of less than 16% among adults is
often used to confirm iron deficiency (93). Among nonpregnant
women of childbearing age, the sensitivity of low transferrin
saturation (less than 16%) for iron deficiency as defined by no
stainable bone marrow iron is 20%, and the specificity is 93%
(93).

The factors that affect serum iron concentration and TIBC,
such as iron status, diurnal variation (87,103), and day-to-day
variation within persons (101), can affect the measured
transferrin saturation as well. The diurnal varation is larger
for transferrin saturation than it is for Hb concentration or Hct
(87,103). Transferrin saturation is an indicator of
iron-deficient erythropoiesis rather than iron depletion; hence,
it is less sensitive to changes in iron stores than is serum
ferritin concentration (30,31). The cost of assessing transferrin
saturation and the unavailability of simple, clinic-based methods
for measuring transferrin saturation hinder the use of this test
in screening for iron deficiency.
JUSTIFICATION FOR RECOMMENDATIONS

These recommendations are intended to guide primary
health-care providers in preventing and controlling iron
deficiency in infants, preschool children, and women of
childbearing age (especially pregnant women). Both primary
prevention through appropriate dietary intake and secondary
prevention through detecting and treating iron-deficiency anemia
are discussed.
Primary Prevention

Primary prevention of iron deficiency means ensuring an
adequate intake of iron. A reliable source of dietary iron is
essential for every infant and child's growth and development,
because a rapid rate of growth and low dietary iron may
predispose an infant to exhaustion of iron stores by ages 4-6
months (23). Primary prevention of iron deficiency is most
important for children aged less than 2 years, because among all
age groups they are at the greatest risk for iron deficiency
caused by inadequate intake of iron (28,45,47,48,91). The
adequacy of the iron content of an infant's diet is a major
determinant of the iron status of the infant as a young child, as
indicated by declines in the prevalence of iron-deficiency anemia
that correspond with improvements in infant feeding practices
(1-3). In infants and young children, iron deficiency may result in
developmental and behavioral disturbances (33,34).

The evidence for the effectiveness of primary prevention
among pregnant women is less clear. Although iron-deficiency
anemia during pregnancy is associated with preterm delivery and
delivering a low-birthweight baby (38), well designed, randomized
control trials are needed to evaluate the effectiveness of
universal iron supplementation on mitigating adverse birth
outcomes. Some studies have indicated that adequate iron
supplementation during pregnancy reduces the prevalence of
iron-deficiency anemia (6,10,39-42,66,104), but over the last few
decades, the recommendation by the Council on Foods and Nutrition
and other groups to supplement iron intake during pregnancy has
not resulted in a reduced prevalence of anemia among low-income,
pregnant women (4,9,105). Evidence on iron supplement use is
limited, however, so it is not known how well the recommendation
has been followed. Conclusive evidence of the benefits of
universal iron supplementation for all women is lacking, but CDC
advocates universal iron supplementation for pregnant women
because a large proportion of women have difficulty maintaining
iron stores during pregnancy and are at risk for anemia
(6,18,63), iron-deficiency anemia during pregnancy is associated
with adverse outcomes (38), and supplementation during pregnancy
is not associated with important health risks (10,65,66).
Potential Adverse Effects of Increasing Dietary Iron Intake

Approximately 3.3 million women of childbearing age and
240,000 children aged 1-2 years have iron-deficiency anemia (45);
conversely, up to one million persons in the United States may be
affected by iron overload due to hemochromatosis (106,107).
Hemochromatosis is a genetic condition characterized by excessive
iron absorption, excess tissue iron stores, and potential tissue
injury. If undetected and untreated, iron overload may eventually
result in the onset of morbidity (e.g., cirrhosis, hepatomas,
diabetes, cardiomyopathy, arthritis or athropathy, or
hypopituitarism with hypogonadism), usually between ages 40 and
60 years. Clinical expression of iron overload depends on the
severity of the metabolic defect, the presence of sufficient
quantities of absorbable iron in the diet, and physiological
blood loss from the body (e.g., menstruation) (16). Transferrin
saturation is the recommended screening test for hemochromatosis;
a repeated high value indicates hemochromatosis (108). Preventing
or treating the clinical signs of hemochromatosis involves
repeated phlebotomy to remove excess iron from the body (108).

Although increases in iron intake would seem contraindicated
in persons with hemochromatosis, there is no evidence that iron
fortification of foods or the use of a recommended iron
supplementation regimen during pregnancy is associated with
increased risk for clinical disease due to hemochromatosis (16).
Even when their dietary intake of iron is approximately average,
persons with iron overload due to hemochromatosis will require
phlebotomy to reduce their body's iron stores (108).
Secondary Prevention

Secondary prevention involves screening for, diagnosing, and
treating iron deficiency. Screening tests can be for anemia or
for earlier indicators of iron deficiency (e.g., erythrocyte
protoporphyrin concentration or serum ferritin concentration).
The cost, feasibility, and variability of measurements other than
Hb concentration and Hct currently preclude their use for
screening. The decision to screen an entire population or to
screen only persons at known risk for iron deficiency should be
based on the prevalence of iron deficiency in that population
(73).

The percentage of anemic persons who are truly iron
deficient (i.e., the positive predictive value of anemia
screening for iron deficiency) increases with increasing
prevalence of iron deficiency in the population (73). In the
United States, children from low-income families, children living
at or below the poverty level, and black or Mexican-American
children are at higher risk for iron deficiency than are children
from middle- or high-income families, children living above the
poverty level, and white children, respectively (2,3,45). Routine
screening for anemia among populations of children at higher risk
for iron deficiency is effective, because anemia is predictive of
iron deficiency. In populations having a low prevalence of anemia
or a prevalence of iron deficiency less than 10% (e.g., children
from middle- or high-income families and white children)
(2,3,45), anemia is less predictive of iron deficiency (73), and
selectively screening only the persons having known risk factors
for iron deficiency increases the positive predictive value of
anemia screening (3,70). Because the iron stores of a full-term
infant of normal or high birthweight can meet the body's iron
requirements up to age 6 months (23), anemia screening is of
little value before age 6 months for these infants.
Anemia among pregnant women and anemia among all nonpregnant
women of childbearing age should be considered together, because
childbearing increases the risk for iron deficiency (both during
and after pregnancy) (41,42), and iron deficiency before
pregnancy likely increases the risk for iron deficiency during
pregnancy (109). Periodic screening for anemia among adolescent
girls and women of childbearing age is indicated for several
reasons. First, most women have dietary intake of iron below the
recommended dietary allowance (46,47). Second, heavy menstrual
blood loss, which increases iron requirements to above the
recommended dietary allowance, affects an estimated 10% of women
of childbearing age (17,18). Finally, the relatively high
prevalence of iron deficiency and iron-deficiency anemia among
nonpregnant women of childbearing age (45) and of anemia among
low-income, pregnant women (4) suggests that periodic screening
for anemia is indicated among adolescent girls and nonpregnant
women of childbearing age during routine medical examinations
(73) and among pregnant women at the first prenatal visit. Among
men and postmenopausal women, in whom iron deficiency and
iron-deficiency anemia are uncommon (45), anemia screening is not
highly predictive of iron deficiency.
RECOMMENDATIONS
Infants (Persons Aged 0-12 Months) and Preschool Children
(Persons Aged 1-5 Years)

Primary prevention of iron deficiency in infants and
preschool children should be achieved through diet. Information
on diet and feeding is available in the Pediatric Nutrition
Handbook (8), Guide to Clinical Preventive Services (10),
Nutrition and Your Health: Dietary Guidelines for Americans (14),
Breastfeeding and the Use of Human Milk (110), and Clinician's
Handbook of Preventive Services: Put Prevention into Practice
(111). For secondary prevention of iron deficiency in this age
group, screening for, diagnosing, and treating iron-deficiency
anemia are recommended.
Primary Prevention
Milk and Infant Formulas

When exclusive breast feeding is stopped, encourage use of an
additional source of iron (approximately 1 mg/kg per day of
iron), preferably from supplementary foods.

For infants aged less than 12 months who are not breast fed or
who are partially breast fed, recommend only iron-fortified
infant formula as a substitute for breast milk.

For breast-fed infants who receive insufficient iron from
supplementary foods by age 6 months (i.e., less than 1 mg/kg per
day), suggest 1 mg/kg per day of iron drops.

For breast-fed infants who were preterm or had a low
birthweight, recommend 2-4 mg/kg per day of iron drops (to a
maximum of 15 mg/day) starting at 1 month after birth and
continuing until 12 months after birth.

Encourage use of only breast milk or iron-fortified infant
formula for any milk-based part of the diet (e.g., in infant
cereal) and discourage use of low-iron milks (e.g., cow's milk,
goat's milk, and soy milk) until age 12 months.

Suggest that children aged 1-5 years consume no more than 24 oz
of cow's milk, goat's milk, or soy milk each day.
Solid Foods

At age 4-6 months or when the extrusion reflex disappears,
recommend that infants be introduced to plain, iron-fortified
infant cereal. Two or more servings per day of iron-fortified
infant cereal can meet an infant's requirement for iron at this
age.

By approximately age 6 months, encourage one feeding per day of
foods rich in vitamin C (e.g., fruits, vegetables, or juice) to
improve iron absorption, preferably with meals.

Suggest introducing plain, pureed meats after age 6 months or
when the infant is developmentally ready to consume such food.
Secondary Prevention
Universal Screening

In populations of infants and preschool children at high risk
for iron-deficiency anemia (e.g., children from low-income
families, children eligible for the Special Supplemental
Nutrition Program for Women, Infants, and Children {WIC},
migrant
children, or recently arrived refugee children), screen all
children for anemia between ages 9 and 12 months, 6 months
later,
and annually from ages 2 to 5 years.
Selective Screening

In populations of infants and preschool children not at high
risk for iron-deficiency anemia, screen only those children who
have known risk factors for the condition. These children are
described in the next three bulleted items.

Consider anemia screening before age 6 months for preterm
infants and low-birthweight infants who are not fed
iron-fortified infant formula.

Annually assess children aged 2-5 years for risk factors for
iron-deficiency anemia (e.g., a low-iron diet, limited access to
food because of poverty or neglect, or special health-care
needs). Screen these children if they have any of these risk
factors.

At ages 9-12 months and 6 months later (at ages 15-18 months),
assess infants and young children for risk factors for anemia.
Screen the following children:

Preterm or low-birthweight infants

Infants fed a diet of non-iron-fortified infant formula
for greater than 2 months

Infants introduced to cow's milk before age 12 months

Breast-fed infants who do not consume a diet adequate in
iron after age 6 months (i.e., who receive insufficient iron
from
supplementary foods)

Children who consume greater than 24 oz daily of cow's
milk

Children who have special health-care needs (e.g.,
children who use medications that interfere with iron
absorption
and children who have chronic infection, inflammatory
disorders,
restricted diets, or extensive blood loss from a wound, an
accident, or surgery).

Diagnosis and Treatment

Check a positive anemia screening result by performing a repeat
Hb concentration or Hct test. If the tests agree and the child
is
not ill, a presumptive diagnosis of iron-deficiency anemia can
be
made and treatment begun.

Treat presumptive iron-deficiency anemia by prescribing 3 mg/kg
per day of iron drops to be administered between meals. Counsel
the parents or guardians about adequate diet to correct the
underlying problem of low iron intake.

Repeat the anemia screening in 4 weeks. An increase in Hb
concentration of greater than or equal to 1 g/dL or in Hct of
greater than or equal to 3% confirms the diagnosis of
iron-deficiency anemia. If iron-deficiency anemia is confirmed,
reinforce dietary counseling, continue iron treatment for 2 more
months, then recheck Hb concentration or Hct. Reassess Hb
concentration or Hct approximately 6 months after successful
treatment is completed.

If after 4 weeks the anemia does not respond to iron treatment
despite compliance with the iron supplementation regimen and the
absence of acute illness, further evaluate the anemia by using
other laboratory tests, including MCV, RDW, and serum ferritin
concentration. For example, a serum ferritin concentration of
less than or equal to 15 ug/L confirms iron deficiency, and a
concentration of greater than 15 ug/L suggests that iron
deficiency is not the cause of the anemia.
School-Age Children (Persons Aged 5- less than 12 Years) and
Adolescent Boys (Males Aged 12- less than 18 Years)

Among school-age children and adolescent boys, only those
who have a history of iron-deficiency anemia, special health-care
needs, or low iron intake should be screened for anemia.
Age-specific anemia criteria should be used (Table_6).
Treatment
for iron-deficiency anemia includes one 60-mg iron tablet each
day for school-age children and two 60-mg iron tablets each day
for adolescent boys and counseling about dietary intake of iron.
Follow-up and laboratory evaluation are the same for school-age
children and adolescent boys as they are for infants and
preschool children.
Adolescent Girls (Females 12- less than 18 Years) and Nonpregnant
Women of Childbearing Age

Primary prevention of iron deficiency for adolescent girls
and nonpregnant women of childbearing age is through diet.
Information about healthy diets, including good sources of iron,
is available in Nutrition and Your Health: Dietary Guidelines for
Americans (14). Screening for, diagnosing, and treating
iron-deficiency anemia are secondary prevention approaches.
Age-specific anemia criteria should be used during screening
(Table_6).
Primary Prevention

Most adolescent girls and women do not require iron
supplements, but encourage them to eat iron-rich foods and foods
that enhance iron absorption.

Women who have low-iron diets are at additional risk for
iron-deficiency anemia; guide these women in optimizing their
dietary iron intake.
Secondary Prevention
Screening

Starting in adolescence, screen all nonpregnant women for
anemia every 5-10 years throughout their childbearing years
during routine health examinations.

Confirm a positive anemia screening result by performing a
repeat Hb concentration or Hct test. If the adolescent girl or
woman is not ill, a presumptive diagnosis of iron-deficiency
anemia can be made and treatment begun.

Treat adolescent girls and women who have anemia by prescribing
an oral dose of 60-120 mg/day of iron. Counsel these patients
about correcting iron deficiency through diet.

Follow up adolescent girls and nonpregnant women of
childbearing age as is done for infants and preschool children,
except that for a confirmed case of iron-deficiency anemia,
continue iron treatment for 2-3 more months.

If after 4 weeks the anemia does not respond to iron treatment
despite compliance with the iron supplementation regimen and the
absence of acute illness, further evaluate the anemia by using
other laboratory tests, including MCV, RDW, and serum ferritin
concentration. In women of African, Mediterranean, or Southeast
Asian ancestry, mild anemia unresponsive to iron therapy may be
due to thalassemia minor or sickle cell trait.
Pregnant Women

Primary prevention of iron deficiency during pregnancy
includes adequate dietary iron intake and iron supplementation.
Information about healthy diets, including good sources of iron,
is found in Nutrition and Your Health: Dietary Guidelines for
Americans (14). More detailed information for pregnant women is
found in Nutrition During Pregnancy and Lactation: An
Implementation Guide (112). Secondary prevention involves
screening for, diagnosing, and treating iron-deficiency anemia.
Primary Prevention

Start oral, low-dose (30 mg/day) supplements of iron at the
first prenatal visit.

Screen for anemia at the first prenatal care visit. Use the
anemia criteria for the specific stage of pregnancy
(Table_6).
Diagnosis and Treatment

Confirm a positive anemia screening result by performing a
repeat Hb concentration or Hct test. If the pregnant woman is
not
ill, a presumptive diagnosis of iron-deficiency anemia can be
made and treatment begun.

If Hb concentration is less than 9.0 g/dL or Hct is less than
27.0%, refer the patient to a physician familiar with anemia
during pregnancy for further medical evaluation.

If after 4 weeks the anemia does not respond to iron treatment
(the woman remains anemic for her stage of pregnancy and Hb
concentration does not increase by 1 g/dL or Hct by 3%) despite
compliance with an iron supplementation regimen and the absence
of acute illness, further evaluate the anemia by using other
tests, including MCV, RDW, and serum ferritin concentration. In
women of African, Mediterranean, or Southeast Asian ancestry,
mild anemia unresponsive to iron therapy may be due to
thalassemia minor or sickle cell trait.

When Hb concentration or Hct becomes normal for the stage of
gestation, decrease the dose of iron to 30 mg/day.

During the second or third trimester, if Hb concentration is
greater than 15.0 g/dL or Hct is greater than 45.0%, evaluate
the
woman for potential pregnancy complications related to poor
blood
volume expansion.
Postpartum Women

Women at risk for anemia at 4-6 weeks postpartum should be
screened for anemia by using a Hb concentration or Hct test. The
anemia criteria for nonpregnant women should be used (Table_6).
Risk factors include anemia continued through the third
trimester, excessive blood loss during delivery, and a multiple
birth. Treatment and follow-up for iron-deficiency anemia in
postpartum women are the same as for nonpregnant women. If no
risk factors for anemia are present, supplemental iron should be
stopped at delivery.
Men (Males Aged greater than or equal to 18 Years) and
Postmenopausal Women

No routine screening for iron deficiency is recommended for
men or postmeno-pausal women. Iron deficiency or anemia detected
during routine medical examinations should be fully evaluated for
its cause. Men and postmenopausal women usually do not need iron
supplements.
CONCLUSION

In the United States, iron deficiency affects 7.8 million
adolescent girls and women of childbearing age and 700,000
children aged 1-2 years (45). Primary health-care providers can
help prevent and control iron deficiency by counseling
individuals and families about sound iron nutrition during
infancy and beyond and about iron supplementation during
pregnancy, by screening persons on the basis of their risk for
iron deficiency, and by treating and following up persons with
presumptive iron deficiency. Implementing these recommendations
will help reduce manifestations of iron deficiency (e.g., preterm
births, low birthweight, and delays in infant and child
development) and thus improve public health.

Anderson SA, ed. Guidelines for the assessment and management
of iron deficiency in women of childbearing age. Bethesda, MD:
U.S. Department of Health and Human Services, Food and Drug
Administration, Center for Food Safety and Applied Nutrition,
1991.

Public Health Service. Caring for our future: the content of
prenatal care. A report of the Public Health Service Expert
Panel
on the Content of Prenatal Care. Washington, DC: U.S.
Department
of Health and Human Services, Public Health Service, 1989.

U.S. Department of Agriculture and U.S. Department of Health
and Human Services. Nutrition and your health: dietary
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